tbuckley/cabot-search huggingface dataset:
Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial
Authors: Kensuke Kataoka, Osamu Nishiyama, Takashi Ogura, Yoshihiro Mori, Ryo Kozu, Shinichi Arizono, Tohru Tsuda, Hiromi Tomioka, Keisuke Tomii, Koji Sakamoto, Hiroshi Ishimoto, Michiko Kagajo, Hiroyuki Ito, Kazuya Ichikado, Hajime Sasano, Seiichirou Eda, Machiko Arita, Yasuhiro Goto, Osamu Hataji, Satoshi Fuke, Ryota Shintani, Hirotsugu Hasegawa, Masahiko Ando, Tomoya Ogawa, Masashi Shiraishi, Fumiko Watanabe, Koichi Nishimura, Takuma Sasaki, Shinjiro Miyazaki, Hideo Saka, Yasuhiro Kondoh
Journal: Thorax (2023)

Background Idiopathic pulmonary fibrosis (IPF) is characterised by worsening dyspnoea and exercise intolerance. Research question Does a long-term pulmonary rehabilitation improve exercise tolerance in patients with IPF treated with standard antifibrotic drugs, which are expected to reduce disease progression? Methods This open-label randomised controlled trial was performed at 19 institutions. Stable patients receiving nintedanib were randomised into pulmonary rehabilitation and control groups (1:1). The pulmonary rehabilitation group underwent initial rehabilitation which included twice-weekly sessions of monitored exercise training for 12 weeks, followed by an at-home rehabilitation programme for 40 weeks. The control group received usual care only, without pulmonary rehabilitation. Both groups continued to receive nintedanib. The primary and main secondary outcomes were change in 6 min walking distance (6MWD) and change in endurance time (using cycle ergometry) at week 52. Results Eighty-eight patients were randomised into pulmonary rehabilitation (n=45) and control (n=43) groups. Changes in 6MWD were −33 m (95% CI −65 to −1) and −53 m (95% CI −86 to −21) in the pulmonary rehabilitation and control groups, respectively, with no statistically significant difference (mean difference, 21 m (95% CI −25 to 66), p=0.38). Changes in endurance time were significantly better in the pulmonary rehabilitation (64 s, 95% CI −42.3 to 171)) than in the control (−123 s (95% CI −232 to −13)) group (mean difference, 187 s (95% CI 34 to 153), p=0.019). Interpretation Although pulmonary rehabilitation in patients taking nintedanib did not improve 6MWD in the long term, it led to prolonged improvement in endurance time. Trial registration number UMIN000026376.
Comparison of Postpartum Opioid Prescriptions Before vs During the COVID-19 Pandemic
Authors: Shelby R. Steuart, Emily C. Lawler, Grace Bagwell Adams, Hailemichael Shone, Amanda J. Abraham
Journal: JAMA Network Open (2023)

Importance The COVID-19 pandemic substantially disrupted routine health care and exacerbated existing barriers to health care access. Although postpartum women frequently experience pain that interferes with activities of daily living, which is often successfully treated with prescription opioid analgesics, they are also at high risk for opioid misuse. Objective To compare postpartum opioid prescription fills after the onset of the COVID-19 pandemic in March 2020 with fills before the pandemic. Design, Setting, and Participants In this cross-sectional study of 460 371 privately insured postpartum women who delivered a singleton live newborn between July 1, 2018, and December 31, 2020, postpartum opioid fills before March 1, 2020, were compared with fills after March 1, 2020. Statistical analysis was performed from December 1, 2021, to September 15, 2022. Exposure COVID-19 pandemic onset in March 2020. Main Outcomes and Measures The main outcome was postpartum opioid fills, defined as patient fills of opioid prescriptions during the 6 months after birth. Opioid prescriptions were explored in terms of 5 measures: mean number of fills per person, mean filled morphine milligram equivalents (MMEs) per day, mean days supplied, percentage of patients filling a prescription for a schedule II opioid, and percentage of patients filling a prescription for a schedule III or higher opioid. Results Among 460 371 postpartum women (mean [SD] age at delivery, 29.0 [10.8] years), those who gave birth to a single, live newborn after March 2020 were 2.8 percentage points more likely to fill an opioid prescription than expected based on the preexisting trend (forecasted, 35.0% [95% CI, 34.0%-35.9%]; actual, 37.8% [95% CI, 36.8%-38.7%]). The COVID-19 period was also associated with an increase in MMEs per day (forecasted mean [SD], 34.1 [2.0] [95% CI, 33.6-34.7]; actual mean [SD], 35.8 [1.8] [95% CI, 35.3-36.3]), number of opioid fills per patient (forecasted, 0.49 [95% CI, 0.48-0.51]; actual, 0.54 [95% CI, 0.51-0.55]), and percentage of patients filling a schedule II opioid prescription (forecasted, 28.7% [95% CI, 27.9%-29.6%]; actual, 31.5% [95% CI, 30.6%-32.3%]). There was no significant association with days’ suppy of opioids per prescription or percentage of patients filling a prescription for a schedule III or higher opioid. Results stratified by delivery modality showed that the observed increases were larger for patients who delivered by cesarean birth than those delivering vaginally. Conclusions and Relevance This cross-sectional study suggests that the onset of the COVID-19 pandemic was associated with significant increases in postpartum opioid fills. Increases in opioid prescriptions may be associated with increased risk of opioid misuse, opioid use disorder, and opioid-related overdose among postpartum women.
Neutral Models of <i>De Novo</i> Gene Emergence Suggest that Gene Evolution has a Preferred Trajectory
Authors: Bharat Ravi Iyengar, Erich Bornberg-Bauer
Journal: Molecular Biology and Evolution (2023)

Abstract New protein coding genes can emerge from genomic regions that previously did not contain any genes, via a process called de novo gene emergence. To synthesize a protein, DNA must be transcribed as well as translated. Both processes need certain DNA sequence features. Stable transcription requires promoters and a polyadenylation signal, while translation requires at least an open reading frame. We develop mathematical models based on mutation probabilities, and the assumption of neutral evolution, to find out how quickly genes emerge and are lost. We also investigate the effect of the order by which DNA features evolve, and if sequence composition is biased by mutation rate. We rationalize how genes are lost much more rapidly than they emerge, and how they preferentially arise in regions that are already transcribed. Our study not only answers some fundamental questions on the topic of de novo emergence but also provides a modeling framework for future studies.
Structural and functional characterization of capsid binding by anti-AAV9 monoclonal antibodies from infants after SMA gene therapy
Authors: Grant J. Logan, Mario Mietzsch, Neeta Khandekar, Arlene D’Silva, Daniel Anderson, Mawj Mandwie, Jane Hsi, Austin R. Nelson, Paul Chipman, Jennifer Jackson, Peter Schofield, Daniel Christ, Christopher C. Goodnow, Joanne H. Reed, Michelle A. Farrar, Robert McKenna, Ian E. Alexander
Journal: Molecular Therapy (2023)

Success in the treatment of infants with spinal muscular atrophy (SMA) underscores the potential of vectors based on adeno-associated virus (AAV). However, a major obstacle to the full realization of this potential is pre-existing natural and therapy-induced anti-capsid humoral immunity. Structure-guided capsid engineering is one possible approach to surmounting this challenge but necessitates an understanding of capsid-antibody interactions at high molecular resolution. Currently, only mouse-derived monoclonal antibodies (mAbs) are available to structurally map these interactions, which presupposes that mouse and human-derived antibodies are functionally equivalent. In this study, we have characterized the polyclonal antibody responses of infants following AAV9-mediated gene therapy for SMA and recovered 35 anti-capsid mAbs from the abundance of switched-memory B (smB) cells present in these infants. For 21 of these mAbs, seven from each of three infants, we have undertaken functional and structural analysis measuring neutralization, affinities, and binding patterns by cryoelectron microscopy (cryo-EM). Four distinct patterns were observed akin to those reported for mouse-derived mAbs, but with early evidence of differing binding pattern preference and underlying molecular interactions. This is the first human and largest series of anti-capsid mAbs to have been comprehensively characterized and will prove to be powerful tools for basic discovery and applied purposes.
Systems, Wrongs, and Moral Aggregation
Authors: Katrina Hutchison
Journal: The American Journal of Bioethics (2023)

"Systems, Wrongs, and Moral Aggregation." The American Journal of Bioethics, 23(4), pp. 24–25This article refers to:Materialized Oppression in Medical Tools and Technologies Additional informationFundingThis work was supported by Australian Research Council (DE200101301, DP200100883); British Academy (VF1\103510).
Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events
Authors: Yu Zuo, Sherwin Navaz, Wenying Liang, Chun Li, Colby R. Ayers, Christine E. Rysenga, Alyssa Harbaugh, Gary L. Norman, E. Blair Solow, Bonnie Bermas, Oludamilola Akinmolayemi, Anand Rohatgi, David R. Karp, Jason S. Knight, James A. de Lemos
Journal: JAMA Network Open (2023)

Importance The prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated. Objective To determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population. Design, Setting, and Participants This cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti–beta-2 glycoprotein I [aβ2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023. Main Outcomes and Measures Associations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons. Results Among the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), aβ2GPI IgM (63 [2.6%]), and aβ2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and aβ2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; aβ2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of aβ2GPI IgA negatively correlated with cholesterol efflux capacity ( r = −0.055; P = .009) and positively correlated with circulating oxidized LDL ( r = 0.055; P = .007). aβ2GPI IgA–positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Conclusions and Relevance In this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and aβ2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.
The impact of varying the number and selection of conditions on estimated multimorbidity prevalence: A cross-sectional study using a large, primary care population dataset
Authors: Clare MacRae, Megan McMinn, Stewart W. Mercer, David Henderson, David A. McAllister, Iris Ho, Emily Jefferson, Daniel R. Morales, Jane Lyons, Ronan A. Lyons, Chris Dibben, Bruce Guthrie
Journal: PLoS Medicine (2023)

Background Multimorbidity prevalence rates vary considerably depending on the conditions considered in the morbidity count, but there is no standardised approach to the number or selection of conditions to include. Methods and findings We conducted a cross-sectional study using English primary care data for 1,168,260 participants who were all people alive and permanently registered with 149 included general practices. Outcome measures of the study were prevalence estimates of multimorbidity (defined as ≥2 conditions) when varying the number and selection of conditions considered for 80 conditions. Included conditions featured in ≥1 of the 9 published lists of conditions examined in the study and/or phenotyping algorithms in the Health Data Research UK (HDR-UK) Phenotype Library. First, multimorbidity prevalence was calculated when considering the individually most common 2 conditions, 3 conditions, etc., up to 80 conditions. Second, prevalence was calculated using 9 condition-lists from published studies. Analyses were stratified by dependent variables age, socioeconomic position, and sex. Prevalence when only the 2 commonest conditions were considered was 4.6% (95% CI [4.6, 4.6] p &lt; 0.001), rising to 29.5% (95% CI [29.5, 29.6] p &lt; 0.001) considering the 10 commonest, 35.2% (95% CI [35.1, 35.3] p &lt; 0.001) considering the 20 commonest, and 40.5% (95% CI [40.4, 40.6] p &lt; 0.001) when considering all 80 conditions. The threshold number of conditions at which multimorbidity prevalence was &gt;99% of that measured when considering all 80 conditions was 52 for the whole population but was lower in older people (29 in &gt;80 years) and higher in younger people (71 in 0- to 9-year-olds). Nine published condition-lists were examined; these were either recommended for measuring multimorbidity, used in previous highly cited studies of multimorbidity prevalence, or widely applied measures of “comorbidity.” Multimorbidity prevalence using these lists varied from 11.1% to 36.4%. A limitation of the study is that conditions were not always replicated using the same ascertainment rules as previous studies to improve comparability across condition-lists, but this highlights further variability in prevalence estimates across studies. Conclusions In this study, we observed that varying the number and selection of conditions results in very large differences in multimorbidity prevalence, and different numbers of conditions are needed to reach ceiling rates of multimorbidity prevalence in certain groups of people. These findings imply that there is a need for a standardised approach to defining multimorbidity, and to facilitate this, researchers can use existing condition-lists associated with highest multimorbidity prevalence.
After PCI and 6 to 18 mo of DAPT, clopidogrel reduced a composite of clinical events vs. aspirin at 6 y
Authors: Ellis W. Lader
Journal: Annals of Internal Medicine (2023)

Source Citation Kang J, Park KW, Lee H, et al. Aspirin versus clopidogrel for long-term maintenance monotherapy after percutaneous coronary intervention: The HOST-EXAM extended study. Circulation. 2023;147:108-17. 36342475
In thrombotic antiphospholipid syndrome, DOACs vs. VKAs increase arterial thrombotic events but not major bleeding
Authors: Efstratios Koutroumpakis, Anita Deswal
Journal: Annals of Internal Medicine (2023)

Source Citation Khairani CD, Bejjani A, Piazza G, et al. Direct oral anticoagulants vs vitamin K antagonists in patients with antiphospholipid syndromes: meta-analysis of randomized trials. J Am Coll Cardiol. 2023;81:16-30. 36328154
Loss of the receptors ER, PR and HER2 promotes USP15-dependent stabilization of PARP1 in triple-negative breast cancer
Authors: Xiaoxiang Sun, Huanyin Tang, Yu Chen, Zhixi Chen, Zhiyi Hu, Zhen Cui, Yaming Tao, Jian Yuan, Yun Fu, Zhigang Zhuang, Qizhi He, Qian Li, Xianghong Xu, Xiaoping Wan, Ying Jiang, Zhiyong Mao
Journal: Nature Cancer (2023)
Acute Effects of Ambient Air Pollution on Asthma Emergency Department Visits in Ten U.S. States
Authors: Jianzhao Bi, Rohan R. D’Souza, Shannon Moss, Niru Senthilkumar, Armistead G. Russell, Noah C. Scovronick, Howard H. Chang, Stefanie Ebelt
Journal: Environmental Health Perspectives (2023)

Previous studies of short-term ambient air pollution exposure and asthma morbidity in the United States have been limited to a small number of cities and/or pollutants and with limited consideration of effects across ages.
Identification of RNA Virus–Derived RdRp Sequences in Publicly Available Transcriptomic Data Sets
Authors: Ingrida Olendraite, Katherine Brown, Andrew E Firth
Journal: Molecular Biology and Evolution (2023)

RNA viruses are abundant and highly diverse and infect all or most eukaryotic organisms. However, only a tiny fraction of the number and diversity of RNA virus species have been catalogued. To cost-effectively expand the diversity of known RNA virus sequences, we mined publicly available transcriptomic data sets. We developed 77 family-level Hidden Markov Model profiles for the viral RNA-dependent RNA polymerase (RdRp)-the only universal "hallmark" gene of RNA viruses. By using these to search the National Center for Biotechnology Information Transcriptome Shotgun Assembly database, we identified 5,867 contigs encoding RNA virus RdRps or fragments thereof and analyzed their diversity, taxonomic classification, phylogeny, and host associations. Our study expands the known diversity of RNA viruses, and the 77 curated RdRp Profile Hidden Markov Models provide a useful resource for the virus discovery community.
Emerging role of statin therapy in the prevention and management of cirrhosis, portal hypertension, and HCC
Authors: Suzanne R. Sharpton, Rohit Loomba
Journal: Hepatology (2023)

Statins, the most widely used lipid-lowering drugs, are increasingly recognized to have pleiotropic effects including anti-inflammatory and antiangiogenic properties as well as effects on fibrogenesis and liver endothelial function. Given these pathophysiological effects, there is a growing interest in clinical use of statins in persons with cirrhosis. In this review, we summarize available data regarding the safety, adverse effects, and pharmacokinetics of statins in cirrhosis. We review clinical evidence, derived primarily from retrospective cohort and population-based studies, on the association between statin use and reduction in risk for hepatic decompensation and mortality in persons with established cirrhosis. We also review evidence to date regarding the effects of statins on portal hypertension and in chemoprevention of HCC. Finally, we highlight ongoing prospective randomized controlled trials that we expect will expand our understanding of the safety, pharmacokinetics, and efficacy of statins in cirrhosis and guide clinical practice.
Unanswered questions in prostate cancer — findings of an international multi-stakeholder consensus by the PIONEER consortium
Authors: Muhammad Imran Omar, Steven MacLennan, Maria J. Ribal, Monique J. Roobol, Konstantinos Dimitropoulos, Thomas van den Broeck, Sara J. MacLennan, Susan Evans Axelsson, Giorgio Gandaglia, Peter-Paul Willemse, Ken Mastris, John Butler Ransohoff, Zsuzsanna Devecseri, Thomas Abbott, Bertrand De Meulder, Anders Bjartell, Alex Asiimwe, James N’Dow, Emma Smith, Karin Plass, Nicolas Mottet, Robert Shepherd, Lisa Moris, Michael Lardas, Nicola Fossati, Karl Pang, Riccardo Campi, Isabella Greco, Mauro Gacci, Sergio Serni, Ragnar Lonnerbro, Alberto Briganti, Daniele Crosti, Roberto Garzonio, Martina Faticoni, Chris Bangma, Eliza Roest, Arjan Breederland, Sebastiaan Remmers, Derya Tilki, Anssi Auvinen, Teemu Murtola, Tapio Visakorpi, Kirsi Talala, Teuvo Tammela, Aino Siltari, Mieke Van Hemelrijck, Katharina Beyer, Stephane Lejeune, Laurence Colette, Simona Caputova, Delielena Poli, Sigrid van Dorp, Sophie Byrne, Luz Fialho, Ashley Rowland, Neo Tapela, Francesco Ugolini, Charles Auffray, Nesrine Taibi, Ayman Hijazy, Albert Saporta, Kai Sun, Shaun Power, Nazanin Zounemat Kermani, Kees van Bochove, Maxim Moinat, Mirella Kalafati, Azadeh Tafreshiha, Chiara Bernini, Kristina Hlavati, Denis Horgan, Louise Fullwood, Marc Holtorf, Doron Lancet, Gabi Bernstein, Sheela Tripathee, Manfred Wirth, Michael Froehner, Beate Brenner, Angelika Borkowetz, Christian Thomas, Friedemann Horn, Kristin Reiche, Markus Kreuz, Andreas Josefsson, Delila Gasi Tandefelt, Jonas Hugosson, Jack Schalken, Henkjan Huisman, Thomas Hofmarcher, Peter Lindgren, Emelie Andersson, Adam Fridhammar, Monica Tames Grijalva, Frank Verholen, Jihong Zong, Todd Williamson, Kumari Chandrawansa, Reg Waldeck, Amanda Bruno, Ronald Herrera, Ekaterina Nevedomskaya, Samuel Fatoba, Niculae Constantinovici, Ateesha Mohamed, Carl Steinbeisser, Monika Maass, Patrizia Torremante, Emmanuelle Dochy, Federica Pisa, Marc Dietrich Voss, Amit Kiran, Kishore Papineni, Jing Wang-silvanto, Robert Snijder, Xuewei Wang, Mark Lambrecht, Russ Wolfinger, Laurent Antoni, Angela Servan, Katie Pascoe, Paul Robinson, Bertrand Jaton, Daniel Bakkard, Heidi Turunen, Olavi Kilkku, Pasi Pohjanjousi, Olli Voima, Liina Nevalaita, Keijo Punakivi, Christian Reich, Sarah Seager, Shilpa Ratwani, Elaine Longden-Chapman, Danny Burke, Muriel Licour, Sarah Payne, Alan Yong, Flavia Lujan, Sophia Le Mare, Jan Hendrich, Michael Bussmann, Guido Juckeland, Daniel Kotik
Journal: Nature Reviews Urology (2023)